Exposición intrauterina a disruptores endocrinos (ftalatos): fuentes de exposición y cuantificación de metabolitos urinarios / Intrauterine exposure to endocrine disruptors (phthalates): sources of exposure and quantification of urinary metabolites

Introducción: Los ftalatos son disruptores endocrinos usados en la fabricación de múltiples productos de la industria, principalmente plásticos. El periodo fetal representa la principal ventana de vulnerabilidad, y la exposición a ftalatos en esta etapa de vida genera efectos adversos fetales y postnatales. El biomarcador más fiable para medición de ftalatos es la orina. Objetivo: Caracterizar las diferentes fuentes de exposición a disruptores endocrinos y cuantificar la concentración urinaria de ftalatos en gestantes. Materiales y métodos: Estudio transversal, observacional y descriptivo que incluye 400 gestantes que asistieron a control prenatal en las instituciones de salud Génesis y Metrosalud (Medellín-Colombia). Se caracterizaron fuentes de exposición, se recolectó muestras de orina de todas las gestantes, y cuantificó la concentración de ftalatos de 38 mujeres. Resultados: Las medias geométricas de ftalato Di(2-ethylhexyl)phthalate(DEHP), Mono-n-butyl phthalate(MnBP), Mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP) y Mono-2-ethyl-5-oxohexyl phthalate(MEOHP) fueron 162,72µg/L, 58,5 µg/L, 33,93µg/L y 31,63µg/L respectivamente. Conclusiones: La mayoría de las gestantes evaluadas han estado expuestas a lo largo de su vida a fuentes potenciales de disruptores endocrinos, presentes en químicos domésticos, tabaco y uso frecuente de cosméticos faciales y corporales. Las concentraciones de MnBP, MEHHP y MEOHP en orina de las participantes, fueron superiores a los hallazgos a nivel mundial.

Introduction: Phthalates are endocrine disruptors used in the manufacture of various industrial products, mainly plastics. The fetal period represents the principal window of vulnerability, and the exposure to Phthalates in this stage of life generates adverse fetal and post-natal effects. The most reliable biomarker for the assessment of Phthalates is urine. Objective: To characterize the different exposure sources of endocrine disruptors and quantify the urinary concentration of Phthalates in pregnant women. Materials and methods: A cross-sectional, observational, and descriptive study which included 400 pregnant women who received prenatal care in the Genesis and Metrosalud health institutions (Medellín-Colombia). Exposure sources were characterized and urine samples were collected from all pregnant women and the Phthalate concentration was quantified in 38 women. Results: The geometric measures of Phthalate Di(2-ethylhexyl)phthalate(DEHP), Mono-n-butyl phthalate(MnBP), Mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP) and Mono-2-ethyl-5-oxohexyl phthalate(MEOHP) were 162.72µg/L, 58.5 µg/L, 33.93µg/L and 31.63µg/L respectively. Conclusions: The majority of pregnant women that were evaluated were exposed to potential sources of endocrine disruptors throughout their life, which are present in household chemicals, tobacco, and frequent use of facial and body cosmetics. The concentrations of MnBP, MEHHP y MEOHP in urine of participants were higher than those found worldwide.

A genome-wide survey of CD4(+) lymphocyte regulatory genetic variants identifies novel asthma genes.

BACKGROUND: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. OBJECTIVE: We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4(+) lymphocytes for association with asthma. METHODS: eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. RESULTS: Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3/GSDMB variants with asthma (combined P = 2.9 × 10(-8)). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N-acetyl-α-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+) lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. CONCLUSIONS: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.

Identification of asthma risk factors in Mexico City in an International Study of Asthma and Allergy in Childhood survey.

The International Study of Asthma and Allergy in Childhood (ISAAC) has assessed the prevalence of asthma, as well as the factors related to the disease in different countries. The aim of this study was to identify asthma risks factors in Mexico City. Data were obtained from questionnaires of children participating in a phase 3b ISAAC survey. Two thousand ninety-eight boys and 2008 girls were recruited in the 6- to 7-year-old group and 3243 boy and 3333 girls were recruited in the 13- to 14-year-old group. Logistic regression was used to determine the asthma risks factors. In the logistic regression for cumulative and current asthma prevalence, the variables allergic rhinitis and atopic dermatitis were the most important risk factors with the highest odds ratios (OR > 1.5; p < 0.05). The use of antibiotics and paracetamol in the first 12 months of life were related to cumulative asthma in both genders in the 6- to 7-year-old group. Contact of pregnant mother with farm animals was positively related with cumulative asthma in boys in the 6- to 7-year-old group. The main factors associated with the cumulative and current prevalence of asthma in both age groups were atopic dermatitis and allergic rhinitis. Future interventions for the prevention and early diagnosis and treatment could be focused in the natural history of the atopic march.